Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

6.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

4.9K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
4.9K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

5.7K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K
Introduction to Fibroblasts01:09

Introduction to Fibroblasts

3.1K
Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.1K
Replicative Cell Senescence02:15

Replicative Cell Senescence

3.6K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Senescent Cafs Mediate Immunosuppression And Drive Breast Cancer Progression

Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression

Jiayu Ye1, John M Baer2, Douglas V Faget1

  • 1Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri.

Cancer Discovery
|April 29, 2024

Related Experiment Videos

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

4.4K
Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles
08:02

Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles

Published on: May 14, 2021

5.6K
Experimental Generation of Carcinoma-Associated Fibroblasts CAFs from Human Mammary Fibroblasts
15:43

Experimental Generation of Carcinoma-Associated Fibroblasts CAFs from Human Mammary Fibroblasts

Published on: October 25, 2011

23.4K

View abstract on PubMed

Summary
This summary is machine-generated.

Senescent cancer-associated fibroblasts (senCAFs) promote breast cancer growth by suppressing natural killer (NK) cell activity. Eliminating senCAFs unleashes NK cells, restricting tumor progression and offering a potential senolytic therapy target.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • The tumor microenvironment (TME) is critical in tumorigenesis, with its gene expression predicting breast cancer outcomes.
  • Cancer-associated fibroblast (CAF) subtypes within the TME have unclear roles in tumor development.
  • Identifying specific CAF roles is crucial for understanding and targeting breast cancer progression.

Purpose of the Study:

  • To identify and characterize a specific subtype of cancer-associated fibroblasts (CAFs) involved in breast tumor progression.
  • To elucidate the mechanism by which these fibroblasts promote tumor growth.
  • To evaluate the therapeutic potential of targeting these cells in breast cancer.

Main Methods:

  • Utilized the MMTV-PyMT;INK-ATTAC (INK) mouse model for breast cancer studies.

Related Experiment Videos

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

4.4K
Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles
08:02

Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles

Published on: May 14, 2021

5.6K
Experimental Generation of Carcinoma-Associated Fibroblasts CAFs from Human Mammary Fibroblasts
15:43

Experimental Generation of Carcinoma-Associated Fibroblasts CAFs from Human Mammary Fibroblasts

Published on: October 25, 2011

23.4K
  • Identified senescent CAFs (senCAFs) in mouse and human breast tumors.
  • Assessed the impact of senCAFs on natural killer (NK) cell cytotoxicity and tumor growth.
  • Investigated senCAF presence and predictive value in various human breast cancer subtypes (HER2+, ER+, triple-negative breast cancer, DCIS).

    • Main Results:

    • Identified a subset of myofibroblast CAFs (myCAFs) as senescent (senCAFs) in breast tumors.
    • Demonstrated that senCAFs secrete extracellular matrix that inhibits NK cell cytotoxicity, promoting tumor growth.
    • Showed that eliminating senCAFs restores NK cell activity and restricts tumor growth.
    • Confirmed senCAF presence in diverse human breast cancers and ductal carcinoma in situ (DCIS), where they correlate with tumor recurrence.

    Conclusions:

    • Senescent cancer-associated fibroblasts (senCAFs) actively promote breast cancer progression by impairing NK cell-mediated anti-tumor immunity.
    • Targeting senCAFs, potentially through senolytic therapies, represents a promising strategy to restrain breast cancer development and recurrence.